tbuckley/cabot-search huggingface dataset:
Changes in heritability: Unpredictable and of limited use
Authors: Stephen M Downes, Jonathan Michael Kaplan
Journal: Behavioral and Brain Sciences (2022)

Abstract We argue that heritability estimates cannot be used to make informed judgments about the populations from which they are drawn. Furthermore, predicting changes in heritability from population changes is likely impossible, and of limited value. We add that the attempt to separate human environments into cultural and non-cultural components does not advance our understanding of the environmental multiplier effect.
(Super-)cultural clustering explains gender differences too
Authors: Lynda G. Boothroyd, Catharine P. Cross
Journal: Behavioral and Brain Sciences (2022)

Abstract The target paper shows how cultural adaptations to ecological problems can underpin “paradoxical” patterns of phenotypic variation. We argue: (1) Gendered social learning is a cultural adaptation to an ecological problem. (2) In evolutionarily novel environments, this adaptation generates arbitrary-gendered outcomes, leading to the paradoxical case of larger sex differences in more gender equal societies.
Doctors call for report of new “tomato flu” outbreak in India to be retracted
Authors: Kamala Thiagarajan
Journal: BMJ (2022)

The limitations of subgroup analyses are well established—false positives due to multiple comparisons, false negatives due to inadequate power, and limited ability to inform individual treatment decisions because patients have multiple characteristics that vary simultaneously. In this article, we apply Bayes’s rule to determine the probability that a positive subgroup analysis is a true positive. From this framework, we derive simple rules to determine when subgroup analyses can be performed as hypothesis testing analyses and thus inform when subgroup analyses should influence how we practice medicine.
Rajindra Singh Gill
Authors: Tina Gill, Narjit Gill, Angela Bhan
Journal: BMJ (2022)

<h3>Background</h3> Low/middle-income countries carry a disproportionate burden of the morbidity and mortality from thermal burns. Nearly 70% of burn deaths worldwide are from thermal burns in India. Delays to medical care are commonplace and an important predictor of outcomes. We sought to understand the role of emergency medical services (EMS) as part of the healthcare infrastructure for thermal burns in India. <h3>Methods</h3> We conducted a prospective observational study of patients using EMS for thermal burns across five Indian states from May to August 2015. Our primary outcome was mortality at 2, 7 and 30 days. We compared observed mortality with expected mortality using the revised Baux score. We used Χ<sup>2</sup> analysis for categorical variables and Wilcoxon two-sample test for continuous variables. ORs and 95% CIs are reported for all modelled predictor variables. <h3>Results</h3> We enrolled 439 patients. The 30-day follow-up rate was 85.9% (n=377). The median age was 30 years; 56.7% (n=249) lived in poverty; and 65.6% (n=288) were women. EMS transported 94.3% of patients (n=399) to the hospital within 2 hours of their call. Median total body surface area (TBSA) burned was 60% overall, and 80% in non-accidental burns. Sixty-eight per cent of patients had revised Baux scores greater than 80. Overall 30-day mortality was 64.5%, and highest (90.2%) in women with non-accidental burns. Predictors of mortality by multivariate regression were TBSA (OR 7.9), inhalation injury (OR 5.5), intentionality (OR 4.7) and gender (OR 2.2). <h3>Discussion</h3> Although EMS rapidly connects critically burned patients to care in India, mortality remains high, with women disproportionally suffering self-inflicted burns. To combat the burn epidemic in India, efforts must focus on rapid medical care and critical care services, and on a burn prevention strategy that includes mental health and gender-based violence support services.
Correlation of gut microbiota and metabolic functions with the antibody response to the BBIBP-CorV vaccine
Authors: Bo Tang, Li Tang, Wei He, Xingyu Jiang, Changjiang Hu, Yicheng Li, Yang Zhang, Kun Pang, Yuanyuan Lei, Shengpeng Li, Shuang Liu, Sumin Wang, Min Yang, Zhongjun Li, Fangqing Zhao, Shiming Yang
Journal: Cell Reports Medicine (2022)

Increasing evidence indicates that gut microbiota may play a key role in vaccination immunity. Here, we investigate whether the human gut microbiota and metabolic function correlate with the BBIBP-CorV vaccine response. A total of 207 participants who received the BBIBP-CorV vaccine are enrolled. The gut microbiome and metabolic functions are investigated using metagenomic sequencing and metabolomic assays. We find that BBIBP-CorV vaccination is accompanied by altered microbiome composition and functional pathways, and the gut microbiome and its functional profiles correlate with the vaccine response. The levels of short-chain fatty acids (SCFAs) are much higher in the high antibody response group compared to the low response group, and several SCFAs display a positive correlation with the antibody response. Our study highlights that the gut microbiome and its function is associated with the BBIBP-CorV vaccine response, providing evidence for further exploration of microbiome modulation to improve COVID-19 vaccine efficacy.
Making Love With Death
Authors: M. Therese Southgate
Journal: JAMA (1986)

In the 21 years since it began its weekly use of a four-color art cover,The Journalhas reproduced some 1,000 paintings and other works of art. Only twice before have we elected to repeat a cover; each time the circumstances were exceptional. This week, for the third time, we repeat a cover, one that was first used almost 20 years ago.<sup>1</sup>Again, the circumstances are exceptional: there does not exist a more eloquent statement on what has become our national tragedy. One hundred years ago, when van Gogh painted<i>Skull With Cigarette</i>, he probably intended a kind of covert self-portrait. In his letters to his brother Theo at that time, Vincent was preoccupied with his health and concerned that he would die before he completed his life's work. He wrote repeatedly of the poor state of his teeth, how it had altered his appearance, ruined his digestion, and
A Biomarker‐Responsive Nanosystem with Colon‐Targeted Delivery for Ulcerative Colitis's Detection and Treatment with Optoacoustic/NIR‐II Fluorescence Imaging
Authors: Zhuo Zeng, Juan Ouyang, Lihe Sun, Fang Zeng, Shuizhu Wu
Journal: Advanced Healthcare Materials (2022)

Abstract Ulcerative colitis (UC) is a prevalent idiopathic inflammatory disease which causes such complications as intestinal perforation, obstruction, and bleeding, and thus deleteriously impacting people's normal work and quality of life. Hence, accurate diagnosis of UC is crucial in terms of planning optimal treatment plan. Herein, a pH/reactive oxygen species (ROS) dual‐responsive nanosystem (BM@EP) is developed for UC's detection and therapy. BM@EP is composed of a chromophore‐drug dyad and the enteric coating. The chromophore‐drug dyad (BOD‐XT‐DHM) is synthesized by linking the chromophore (BOD‐XT‐BOH) and a flavonoid drug (dihydromyricetin DHM) through boronate ester bond. The enteric coating includes Eudragit S100 and poly(lactic‐ co ‐glycolic acid) (PLGA), the former is commonly employed as a pH‐dependent polymer coating excipient so as to attain colon‐targeted delivery, and the latter has been widely used as an excipient for the controlled‐extended release. After oral administration, BM@EP delivers the dyad (BOD‐XT‐DHM) into the colon and releases the dyad molecules by being triggered by the alkaline pH in t colon, thereafter upon being stimulated by overexpressed H 2 O 2 in the inflamed colon, the boronate bond in the dyad is broken down and correspondingly the drug DHM is released for UC therapy, simultaneously the chromophore is released for near‐infrared second window (NIR‐II) fluorescence and optoacoustic imaging for UC diagnosis and recovery evaluation.
Global, regional, and national burdens of HIV and other sexually transmitted infections in adolescents and young adults aged 10–24 years from 1990 to 2019: a trend analysis based on the Global Burden of Disease Study 2019
Authors: Jing Zhang, Bing Ma, Xu Han, Shuangning Ding, Yongze Li
Journal: The Lancet Child & Adolescent Health (2022)
Risk factors for Crimean-Congo Haemorrhagic Fever (CCHF) virus exposure in farming communities in Uganda
Authors: Stella A. Atim, Shirin Ashraf, Sandra Belij-Rammerstorfer, Anna R Ademun, Patrick Vudriko, Teddy Nakayiki, Marc Niebel, James Shepherd, Stephen Balinandi, Gladys Nakanjako, Andrew Abaasa, Paul C.D. Johnson, Steven Odongo, Martin Esau, Milton Bahati, Pontiano Kaleebu, Julius J Lutwama, Charles Masembe, Teresa Lambe, Emma C. Thomson, Robert Tweyongyere
Journal: Journal of Infection (2022)

BackgroundCrimean-Congo Haemorrhagic Fever (CCHF) is an emerging human-health threat causing sporadic outbreaks in livestock farming communities. However, the full extent and the risks associated with exposure of such communities has not previously been well-described.MethodsWe collected blood samples from 800 humans, 666 cattle, 549 goats and 32 dogs in districts within and outside Ugandan cattle corridor in a cross-sectional survey, and tested for CCHFV-specific IgG antibodies using Enzyme-Linked Immunosorbent Assays. Sociodemographic and epidemiological data were recorded using structured questionnaire. Ticks were collected to identify circulating nairoviruses by metagenomic sequencing.ResultsCCHFV seropositivity was in 221/800 (27·6%) in humans, 612/666 (91·8%) in cattle, 413/549 (75·2%) in goats and 18/32 (56·2%) in dogs. Human seropositivity was associated with livestock farming (AOR=5·68, p<0·0001), age (AOR=2·99, p=0·002) and collecting/eating engorged ticks (AOR=2·13, p=0·004). In animals, seropositivity was higher in cattle versus goats (AOR=2·58, p<0·0001), female sex (AOR=2·13, p=0·002) and heavy tick infestation (>50 ticks: AOR=3·52, p=0·004). CCHFV was identified in multiple tick pools of Rhipicephalus appendiculatus.InterpretationThe very high CCHF seropositivity especially among livestock farmers and multiple regional risk factors associated exposures, including collecting/eating engorged ticks previously unrecognised, highlights need for further surveillance and sensitisation and control policies against the disease.
Late-stage cascade of oxidation reactions during the biosynthesis of oxalicine B in Penicillium oxalicum
Authors: Tao Zhang, Guowei Gu, Guodong Liu, Jinhua Su, Zhilai Zhan, Jianyuan Zhao, Jinxiu Qian, Guowei Cai, Shan Cen, Dewu Zhang, Liyan Yu
Journal: Acta Pharmaceutica Sinica B (2022)

Oxalicine B (1) is an α-pyrone meroterpenoid with a unique bispirocyclic ring system derived from Penicillium oxalicum. The biosynthetic pathway of 15-deoxyoxalicine B (4) was preliminarily reported in Penicilliumcanescens, however, the genetic base and biochemical characterization of tailoring reactions for oxalicine B (1) has remained enigmatic. In this study, we characterized three oxygenases from the metabolic pathway of oxalicine B (1), including a cytochrome P450 hydroxylase OxaL, a hydroxylating Fe(II)/α-KG-dependent dioxygenase OxaK, and a multifunctional cytochrome P450 OxaB. Intriguingly, OxaK can catalyze various multicyclic intermediates or shunt products of oxalicines with impressive substrate promiscuity. OxaB was further proven via biochemical assays to have the ability to convert 15-hydroxdecaturin A (3) to 1 with a spiro-lactone core skeleton through oxidative rearrangement. We also solved the mystery of OxaL that controls C-15 hydroxylation. Chemical investigation of the wild-type strain and deletants enabled us to identify 10 metabolites including three new compounds, and the isolated compounds displayed potent anti-influenza A virus bioactivities exhibiting IC50 values in the range of 4.0-19.9 μmol/L. Our studies have allowed us to propose a late-stage biosynthetic pathway for oxalicine B (1) and create downstream derivatizations of oxalicines by employing enzymatic strategies.
Bias by censoring for competing events in survival analysis
Authors: Maarten Coemans, Geert Verbeke, Bernd Döhler, Caner Süsal, Maarten Naesens
Journal: BMJ (2022)

In survival analysis, competing events preclude the occurrence of the event of interest. The censoring of competing events is common in medical studies but leads to biased cumulative incidence estimators. Competing risks methods, such as the non-parametric Aalen-Johansen method or the semi-parametric Fine and Gray model, alleviate this bias and should be preferred above the Kaplan-Meier method and the Cox model, respectively. As an illustrative example, in a large European cohort, we report on the differences in the cumulative incidence estimates of graft failure after kidney transplantation, caused by censoring for recipient death.
Cervical Osteomyelitis
Authors: Matthew A. Parker
Journal: JAMA (1978)

VERTEBRAL bodies are frequent sites of pyogenic osteomyelitis in the adult.<sup>1-3</sup>Anatomically, lumbar vertebrae are most commonly involved, followed by thoracic and, rarely, cervical vertebrae. In most series, vertebral osteomyelitis occurs in the setting of urinary tract disease<sup>2,4,5</sup>or intravenous (IV) drug use.<sup>2,3</sup> The preponderant pathogen in pyogenic osteomyelitis is<i>Staphylococcus aureus</i>,<sup>1,2</sup>followed by Gram-negative rods usually from a urinary tract focus.<sup>5</sup><i>Staphylococcus epidermidis</i>is a rare cause of osteomyelitis.<sup>4,5</sup>The first report of osteomyelitis in hemodialysis patients implicated<i>S epidermidis</i>in three of five cases, either as the sole etiologic agent or combined with<i>S aureus</i>or<i>Pseudomonas aeruginosa</i>.<sup>6</sup>We describe two cases of cervical osteomyelitis due to<i>S epidermidis</i>in long-term hemodialysis patients. <h3>Report of Cases</h3><h3>Case 1.—</h3> A 42-year-old man was admitted in February 1976, with complaints of neck and shoulder pains of three days' duration. He had a history
Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa
Authors: Michelle S. Kim, Daphne Naidoo, Ujani Hazra, Melanie H. Quiver, Wenlong C. Chen, Corinne N. Simonti, Paidamoyo Kachambwa, Maxine Harlemon, Ilir Agalliu, Shakuntala Baichoo, Pedro Fernandez, Ann W. Hsing, Mohamed Jalloh, Serigne M. Gueye, Lamine Niang, Halimatou Diop, Medina Ndoye, Nana Yaa Snyper, Ben Adusei, James E. Mensah, Afua O. D. Abrahams, Richard Biritwum, Andrew A. Adjei, Akindele O. Adebiyi, Olayiwola Shittu, Olufemi Ogunbiyi, Sikiru Adebayo, Oseremen I. Aisuodionoe-Shadrach, Maxwell M. Nwegbu, Hafees O. Ajibola, Olabode P. Oluwole, Mustapha A. Jamda, Elvira Singh, Audrey Pentz, Maureen Joffe, Burcu F. Darst, David V. Conti, Christopher A. Haiman, Petrus V. Spies, André van der Merwe, Thomas E. Rohan, Judith Jacobson, Alfred I. Neugut, Jo McBride, Caroline Andrews, Lindsay N. Petersen, Timothy R. Rebbeck, Joseph Lachance
Journal: Genome biology (2022)

Abstract Background Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how well genetic predictions perform in different populations, we evaluated test characteristics of PRS from three previous studies using data from the UK Biobank and a novel dataset of 1298 prostate cancer cases and 1333 controls from Ghana, Nigeria, Senegal, and South Africa. Results Allele frequency differences cause predicted risks of prostate cancer to vary across populations. However, natural selection is not the primary driver of these differences. Comparing continental datasets, we find that polygenic predictions of case vs. control status are more effective for European individuals (AUC 0.608–0.707, OR 2.37–5.71) than for African individuals (AUC 0.502–0.585, OR 0.95–2.01). Furthermore, PRS that leverage information from African Americans yield modest AUC and odds ratio improvements for sub-Saharan African individuals. These improvements were larger for West Africans than for South Africans. Finally, we find that existing PRS are largely unable to predict whether African individuals develop aggressive forms of prostate cancer, as specified by higher tumor stages or Gleason scores. Conclusions Genetic predictions of prostate cancer perform poorly if the study sample does not match the ancestry of the original GWAS. PRS built from European GWAS may be inadequate for application in non-European populations and perpetuate existing health disparities.
Reply
Authors: Francesco Vizzutti, Ciro Celsa, Salvatore Battaglia, Roberto Miraglia, Marco Enea, Fabio Marra, Antonio Colecchia, Calogero Cammà, Filippo Schepis
Journal: Hepatology (2022)

We appreciated the comments by Liu and colleagues on our recent article.1 As already discussed in the paper, the overall performance of prognostic models commonly employed to predict the outcome of patients with cirrhosis, including the Model for End‐Stage Liver Disease,2 is largely unsatisfactory both in terms of accuracy and calibration. In our study, a competing risks survival analysis was performed,3 with orthotopic liver transplant (OLT) and death for extrahepatic causes considered as competing events for liver‐related death in the overall cohort. OLT was not considered as a competing event for death in the older adult cohort given that OLT is generally not recommended in patients older than 70 years in Europe. Indeed, in our cohort, no older adult patient received OLT. Therefore, we do not believe that this could significantly affect the performance of our model. Moreover, transplant‐free survival was not significantly different in the first five years of follow up comparing the two cohorts. The incorporation of serum liver enzymes and comorbidities such as systemic hypertension did not improve the accuracy of our prognostic model. Moreover, in our study, the prevalence of comorbidities such as diabetes, chronic kidney disease, coronary heart disease, and chronic obstructive pulmonary disease did not significantly differ between younger and older adult patients. As discussed in the paper, this was probably due to the application of stringent inclusion criteria in older adults. It is therefore very unlikely that the variables employed in our model were influenced by comorbidities, although the performance of the model in less stringently selected patients remains to be assessed. Finally, our study included only Caucasian subjects mainly with alcohol (36%) and viral (27%) etiologies. Thus, these results obviously remain to be confirmed in other ethnicities with different prevalence of cirrhosis etiologies.4 Prediction of prognosis in patients with decompensated cirrhosis treated with transjugular intrahepatic portosystemic shunt is challenging. For this reason, further studies with the incorporation of covariates related to the nutritional status and sarcopenia, cardiovascular parameters, inflammation, and intestinal microbiota are warranted.
Breathable, antifreezing, mechanically skin-like hydrogel textile wound dressings with dual antibacterial mechanisms
Authors: Sihan Jiang, Jiajia Deng, Yuhui Jin, Bo Qian, Wanqi Lv, Qiangqiang Zhou, Enhua Mei, Rasoul Esmaeely Neisiany, Yuehua Liu, Zhengwei You, Jie Pan
Journal: Bioactive Materials (2022)

Hydrogels are emerging as the most promising dressings due to their excellent biocompatibility, extracellular matrix mimicking structure, and drug loading ability. However, existing hydrogel dressings exhibit limited breathability, poor environmental adaptability, potential drug resistance, and limited drug options, which extremely restrict their therapeutic effect and working scenarios. Here, the current research introduces the first paradigm of hydrogel textile dressings based on novel gelatin glycerin hydrogel (glyhydrogel) fibers fabricated by the Hofmeister effect based wet spinning. Benefiting from the unique knitted structure, the textile dressing features excellent breathability (1800 times that of the commercially available 3 M dressing) and stretchability (535.51 ± 38.66%). Furthermore, the glyhydrogel textile dressing can also withstand the extreme temperature of -80 °C, showing the potential for application in subzero environments. Moreover, the introduction of glycerin endows the textile dressing with remarkable antibacterial property and expands the selection of loaded drugs (e.g., clindamycin). The prepared glyhydrogel textile dressing shows an excellent infected wound healing effect with a complete rat skin closure within 14 days. All these functions have not been achievable by traditional hydrogel dressings and provide a new approach for the development of hydrogel dressings.
A tumor cell membrane-coated self-amplified nanosystem as a nanovaccine to boost the therapeutic effect of anti-PD-L1 antibody
Authors: Zhilin Li, Hao Cai, Zhiqian Li, Long Ren, Xuelei Ma, Hongyan Zhu, Qiyong Gong, Hu Zhang, Zhongwei Gu, Kui Luo
Journal: Bioactive Materials (2022)

To improve the response rate of immune checkpoint inhibitors such as anti-PD-L1 antibody in immunosuppressive cancers like triple-negative breast cancer (TNBC), induction of immunogenic cell death (ICD) at tumor sites can increase the antigenicity and adjuvanticity to activate the immune microenvironment so that tumors become sensitive to the intervention of immune checkpoint inhibitors. Herein, a self-amplified biomimetic nanosystem, mEHGZ, was constructed by encapsulation of epirubicin (EPI), glucose oxidase (Gox) and hemin in ZIF-8 nanoparticles and coating of the nanoparticles with calreticulin (CRT) over-expressed tumor cell membrane. EPI acts as an ICD inducer, Gox and hemin medicate the cascade generation of reactive oxygen species (ROS) to strengthen the ICD effect, and CRT-rich membrane as "eat me" signal promote presentation of the released antigens by dendritic cells (DCs) to invoke the tumor-immunity cycle. The biomimetic delivery system displays an amplified ICD effect via Gox oxidation, hydroxyl radical generation and glutathione (GSH) depletion. The induced potent ICD effect promotes DCs maturation and cytotoxic T lymphocytes (CTLs) infiltration, reversing an immunosuppressive tumor microenvironment to an immunoresponsive one. Treatment with the nanosystem in combination with anti-PD-L1 antibody results in distinctive inhibition of tumor growth and lung metastasis, supporting that a potent ICD effect can significantly boost the therapeutic efficacy of the anti-PD-L1 antibody. This self-amplified biomimetic nanoplatform offers a promising means of raising the response rate of immune checkpoint inhibitors.
Models of gene–culture evolution are incomplete without incorporating epigenetic effects
Authors: Gillian Ragsdale, Robert Andrew Foley
Journal: Behavioral and Brain Sciences (2022)

Abstract Epigenetics impacts gene–culture coevolution by amplifying phenotypic variation, including clustering, and bridging the difference in timescales between genetic and cultural evolution. The dual inheritance model described by Uchiyama et al. could be modified to provide greater explanatory power by incorporating epigenetic effects.
Understanding cultural clusters: An ethnographic perspective
Authors: Polly Wiessner
Journal: Behavioral and Brain Sciences (2022)

Abstract The cultural evolutionary approach to the dynamics of cumulative culture is insufficient for understanding how culture affects heritability estimates; it ignores the agency of individuals and internal complexity of social groups that drive cultural evolution. Both environmental and social selection need consideration. The WEIRD (western, educated, industrialized, rich, and democratic) problem has never plagued anthropology: A wealth of ethnography is available for the problem at hand.